SIDE EFFECTS

QT prolongation has been reported with KYTRIL [see WARNINGS AND PRECAUTIONS and DRUG INTERATIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in patients.

Chemotherapy-Induced Nausea and Vomiting

The following have been reported during controlled clinical trials or in the routine management of patients. The percentage figures are based on clinical trial experience only. Table 1 gives the comparative frequencies of the two most commonly reported adverse reactions ( ≥ 3%) in patients receiving KYTRIL Injection, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following KYTRIL Injection administration. Reactions were generally recorded over seven days post-KYTRIL Injection administration.

Table 1: Principal Adverse Reactions in Clinical Trials - Single-Day Chemotherapy

Additional adverse events reported in clinical trials were asthenia, somnolence and diarrhea.

In over 3,000 patients receiving KYTRIL Injection (2 to 160 mcg/kg) in single-day and multiple-day clinical trials with emetogenic cancer therapies, adverse events, other than those adverse reactions listed in Table 1, were observed; attribution of many of these events to KYTRIL is uncertain.

Hepatic: In comparative trials, mainly with cisplatin regimens, elevations of AST and ALT ( > 2 times the upper limit of normal) following administration of KYTRIL Injection occurred in 2.8% and 3.3% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2.1%; ALT: 2.4%).

Cardiovascular: Hypertension (2%); hypotension, arrhythmias such as sinus bradycardia, atrial fibrillation, varying degrees of A-V block, ventricular ectopy including non-sustained tachycardia, and ECG abnormalities have been observed rarely.

Central Nervous System: Agitation, anxiety, CNS stimulation and insomnia were seen in less than 2% of patients. Extrapyramidal syndrome occurred rarely and only in the presence of other drugs associated with this syndrome.

Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylaxis, shortness of breath, hypotension, urticaria) have been reported.

Other: Fever (3%), taste disorder (2%), skin rashes (1%). In multiple-day comparative studies, fever occurred more frequently with KYTRIL Injection (8.6%) than with comparative drugs (3.4%, P < 0.014), which usually included dexamethasone.

Postoperative Nausea and Vomiting

The adverse reactions listed in Table 2 were reported in ≥ 2% of adults receiving KYTRIL Injection 1 mg during controlled clinical trials.

Table 2: Adverse Reactions in Controlled Clinical Trials in Postoperative Nausea and Vomiting (Reported in ≥ 2% of Adults Receiving KYTRIL Injection 1 mg)

Additional adverse events reported in clinical trials were constipation, anemia, insomnia, bradycardia, leukocytosis, anxiety, hypotension, infection, hypertension, and urinary tract infection.

In a clinical study conducted in Japan, the types of adverse events differed notably from those reported above in Table 2. The adverse events in the Japanese study that occurred in ≥ 2% of patients and were more frequent with KYTRIL 1 mg than with placebo were: fever (56% to 50%), sputum increased (2.7% to 1.7%), and dermatitis (2.7% to 0%).

Postmarketing Experience

The following adverse reactions have been identified during post approval use of KYTRIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to KYTRIL exposure.

QT prolongation has been reported with KYTRIL [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]

Read the entire FDA prescribing information for Kytril Injection (Granisetron Hydrochloride) »